Small intestine permeability is frequently altered in
inflammatory bowel diseases and may be caused by the translocation of intestinal toxins through leaky small intestine tight junctions (TJs) and adherence. Thus, the aim of the present study was to examine the effects of
thalidomide treatment on the permeability and structure of small intestine TJs in an animal model of experimental
colitis induced by
dinitrobenzene sulfonic acid (
DNBS). Four days after
colitis induction with
DNBS, the ileal TJs were studied by means of transmission electron microscopy using
lanthanum nitrate and immunohistochemistry of
occludin and zonula occludens 1. When compared with
DNBS-treated mice,
thalidomide-treated (200 mg/kg orally starting 30 min after the administration of
DNBS) mice subjected to
DNBS-induced
colitis experienced a significantly reduced rate of the extent and severity of the histological signs of colon injury associated with a significant reduction of plasma and colon
tumor necrosis factor alpha levels. After administration of
DNBS to the mice induced a significant increase of ileal permeability was observed. Distal
colitis in mice induced an increase of TJ permeability throughout the entire small intestine, and the extent of alterations correlates with colonic damage. In particular, we have observed that
thalidomide treatment resulted in a significant reduction of the following: (1) the degree of colon injury, (2) the alteration of zonula occludens 1 and
occludin localization (immunohistochemistry), and (3) intestinal permeability caused by
DNBS in the colon. Taken together, our results clearly show that
thalidomide treatment reduced small intestinal permeability in experimental
colitis through the regulation of TJ
protein.